Uncovering Early Response of Gene Regulatory Networks in ESCs by Systematic Induction of Transcription Factors

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2009 Oct 3

PMID 19796622

Citations 119

Authors

Akira Nishiyama

Li Xin

Alexei A Sharov

Marshall Thomas

Gregory Mowrer

Emily Meyers

Yulan Piao

Samir Mehta

Sarah Yee

Yuhki Nakatake

Carole Stagg

Lioudmila Sharova

Lina S Correa-Cerro

Uwem Bassey

Hien Hoang

Eugene Kim

Richard Tapnio

Yong Qian

Dawood Dudekula

Michal Zalzman

Manxiang Li

Geppino Falco

Hsih-Te Yang

Sung-Lim Lee

Manuela Monti

Ilaria Stanghellini

Md Nurul Islam

Ramaiah Nagaraja

Ilya Goldberg

Weidong Wang

Dan L Longo

David Schlessinger

Minoru S H Ko

Affiliations

Soon will be listed here.

Abstract

To examine transcription factor (TF) network(s), we created mouse ESC lines, in each of which 1 of 50 TFs tagged with a FLAG moiety is inserted into a ubiquitously controllable tetracycline-repressible locus. Of the 50 TFs, Cdx2 provoked the most extensive transcriptome perturbation in ESCs, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. ChIP-Seq revealed that CDX2 binds to promoters of upregulated target genes. By contrast, genes downregulated by CDX2 did not show CDX2 binding but were enriched with binding sites for POU5F1, SOX2, and NANOG. Genes with binding sites for these core TFs were also downregulated by the induction of at least 15 other TFs, suggesting a common initial step for ESC differentiation mediated by interference with the binding of core TFs to their target genes. These ESC lines provide a fundamental resource to study biological networks in ESCs and mice.

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